Erbin and ErbB2 play roles in the sexual differentiation of the song system nucleus HVC in bengalese finches (Lonchura Striata var. domestica)

Abstract

Song control nuclei have distinct sexual differences in songbirds. However, the mechanism that underlies the sexual differentiation of song nuclei is still not well understood. Using a combination of anatomical, pharmacological, genetic, and behavioral approaches, the present study investigated the role of erbb2 (a homolog of the avian erythroblastic leukemia viral oncogene homolog 2) and the erbb2-interacting gene, erbin, in the sexual differentiation of the song nucleus HVC in the Bengalese finch. We first found that both erbin and erbb2 were expressed in the developing HVC at posthatch day (PHD) 15 in a male-biased fashion using qRT-PCR and in situ hybridization. Following the addition of a pharmaceutical inhibitor of the ErbB2 signaling pathway to the culture medium, cell proliferation in the cultured ventricle zone (VZ) that overlies the developing HVC decreased significantly. After the injection of erbin-or erbb2-interfering lentiviruses into the HVC and its overlying VZ at PHD 15, the cell proliferation in the VZ at PHD 24, the number of the differentiated neurons (Hu 1 /BrdU 1 or NeuN 1 /BrdU 1 ) in the HVC at PHD 31 or PHD 130, and the number of RAprojecting cells at PHD 130 all decreased significantly. Additionally, the adult songs displayed serious abnormalities. Finally, 173 male-biased genes were expressed in the developing HVC at PHD 15 using cDNA microarrays, of which 27.2% were Z-linked genes and approximately 20 genes were involved in the Erbin-or ErbB2-related signaling pathways. Our results provide some specific genetic factors that contribute to neurogenesis and sex differentiation in a song nucleus of songbirds.

The effects of Wnt, BMP, and Notch signaling pathways on cell proliferation and neural differentiation in a song control nucleus (HVC) of Lonchura striata

“…Our study and other reports indicate that the sexual differentiation of the HVC includes at least two processes, that is, cell proliferation in the VZ where HVC progenitors are produced and neural differentiation toward HVC neurons (Alvarez‐Buylla et al., 1994; Alvarez‐Buylla & Nottebohm, 1988; Burek et al., 1994; Chen et al., 2014; Zeng et al., 2007; Zhao et al., 2018). Estrogen, a brain‐derived neurotrophic factor, can partly masculinize the female HVC by changing the activities of the two processes (Arnold, 2003; Carruth et al., 2002; Chen et al., 2014; Hartog et al., 2009; Rasika et al., 1999).…”

“…Our study examined the effect of Wnt, Bmp, and Notch signaling pathways on cell proliferation in the VZ overlying the developing HVC and on neural differentiation toward HVC neurons at PHD 15. Brain explants containing male or female HVC were taken using the same method used in our two previous reports (Chen et al., 2014; Zhao et al., 2018). Our results first indicated that β‐catenin in the Wnt signaling pathway was expressed in a sexually different way.…”

“…Estrogen, a brain‐derived neurotrophic factor, can partly masculinize the female HVC by changing the activities of the two processes (Arnold, 2003; Carruth et al., 2002; Chen et al., 2014; Hartog et al., 2009; Rasika et al., 1999). In addition, a Z chromosome‐linked gene, Erbin, is also involved in the sex differentiation of HVC in cell proliferation (Zhao et al., 2018). The present study indicates that Wnt, Bmp, and Notch signaling pathways have effects on cell proliferation in the VZ overlying the developing HVC, and on neural differentiation toward neurons in male HVC.…”

“…To our knowledge, although the neural mechanism of how sexual differences in cell proliferation in the VZ and neural differentiation toward neurons has been studied (Ball & Balthazart, 2020;Beach & Wade, 2015), it is not yet very clear. By using suppression subtraction hybridization or cDNA microarrays, some male-biased genes were identified in the developing HVC at PHD 15, including Erbin (ErbB2interacting protein) or its related genes in the TGF beta signaling pathway (such as Smad1, 2, 3, and 7) (Zhao et al, 2018). It has been shown that Erbin suppresses activin/Smad2dependent induction of endogenous gene expression, and Erbin physically sequesters Smad2/Smad3 from their association with Smad4, negatively modulating TGF beta-dependent transcriptional responses and cell growth inhibition (Dai et al, 2007;Dan et al, 2010;Sflomos et al, 2011).…”

Investigating Nrg1 Signaling in the Regenerating Axolotl Spinal Cord Using Multiplexed FISH

“…However, more research is needed in adult animals to determine differences between age, size, and an animal’s ability to regenerate. Previous studies noted the pro‐survival effect of the Nrg1 pathway on nervous cells during neurodegenerative diseases and SCI (Zhang et al , ; ; Modol‐Caballero et al , ) as well as its effect on remyelination (Taveggia et al , ; Fricker et al , ) and stem cell proliferation and differentiation (Ghashghaei et al , ; Sato et al , ; Reeve et al , ; Zhao et al , ). This well‐documented role of Nrg1 in pro‐regenerative processes in the nervous system led us to suspect that it could contribute to spinal cord regeneration in the highly regenerative axolotl salamander.…”